LD50 values and selenium concentration in rabbit organs after parenteral administration of sodium selenite and determination of toxicity of urososelevit pro inj]

The LD50-values of sodium selenite after i/m injection to rabbits was determined by means of probit-regression straight line. Simultaneously a combination of vitamin E and sodium selenite was tested for toxicity in order to examine the effect of vitamin E on the selenium toxicity. The LD50/24h was 2.53 mg sodium selenite/kg body mass and in combination with vitamin E (30 IU vitamin E/5 mg NaSeO3) 2.73 mg/kg. Furthermore the selenium concentration was determined in blood, liver, kidney and muscles of animals which died or were killed after 24 h respectively. Not only chemical analysis but also relations of time-dose-efficiency and significantly increased LD50-values show a certain protective effect of vitamin E on selenium intoxication.     

A comparative study of the pharmacokinetics of thiopental in the rabbit, sheep and dog

The central arterial pharmacokinetics of thiopental were studied in six rabbits, six sheep and six dogs after a short infusion at approximately 10 mg/kg min. Thiopental was infused to a defined electro-encephalographic endpoint (EEG burst suppression). The time to reach early burst suppression was longer in the dog (3.9 +/- 0.5 min) compared with the sheep (3.0 +/- 0.6 min) and the rabbit (2.5 +/- 0.5 min). The total dose required to produce the same level of EEG activity was higher in the dog (35.9 +/- 6.8 mg/kg) compared with the sheep (24.3 +/- 5.3 mg/kg) and the rabbit (21.6 +/- 6.8 mg/kg). The plasma concentration-time data for each animal was fitted using non-linear regression to a bi- or tri-exponential function. In all animals, the plasma-time profile was best described as a tri-exponential decay. The initial volume of distribution was similar in all three species (rabbit, 38.6 +/- 10.0 mg/kg; sheep, 44.5 +/- 9.1 ml/kg; dog, 38.1 +/- 18.4 ml/kg). The maximum arterial plasma thiopental concentration achieved at EEG burst suppression was higher in the sheep (221.8 +/- 27.9 micrograms/ml) than the dog (164.7 +/- 29.9 micrograms/ml) or the rabbit (112.3 +/- 15.1 micrograms/ml). Thiopental distribution clearance was slower in the sheep (43.6 +/- 15.1 ml/min/kg) compared with the rabbit (110.5 +/- 18.7 ml/min kg) and the dog (97.2 +/- 47.2 ml/min kg). Elimination half-life was extended in the sheep (251.9 +/- 107.8 min) and dog (182.4 +/- 57.9 min) relative to the rabbit (43.1 +/- 3.4 min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of nickel supply on the fattening performance and several biochemical parameters of broiler chickens and rabbits

Broiler chicken and rabbit experiments were carried out to study the effects of nickel (Ni) supplementation on growth performance and Ni metabolism. ROSS cockerels and New Zealand White female rabbits were fed a diet containing Ni in concentrations of 0, 50 and 500 mg/kg in dry matter (DM). Dietary supplementation of 50 mg Ni/kg slightly improved the body weight gain (BWG) and had a beneficial effect on the feed conversion efficiency (FCE) in broiler chickens. However, Ni added at a level of 500 mg/kg significantly (P < 0.05) reduced the BWG by 10% and resulted in significantly (P < 0.05) worse (2.3 +/- 0.2 kg/kg) FCE. The relative weight of the liver in cockerels was significantly (P < 0.05) decreased by Ni as compared to the control group (1.7 and 2.1% vs. 2.6%). The activity of AST and CHE enzymes was increased insignificantly by dietary supplementation of 500 mg Ni/kg, indicating damage of the liver parenchyma. The results of serum biochemistry were confirmed by a mild or moderate form of pathological focal fatty infiltration of the liver in broilers. Supplemental Ni of 50 mg/kg concentration resulted in non-significantly increased BWG in rabbits. Ni added to the diet at a level of 500 mg/kg reduced the digestibility of crude protein by 3-4% and that of crude fibre by 20-25% in rabbits. Approx. 98% of the ingested Ni was lost from the body via the faeces, 0.5-1.5% via the urine and approx. 1% was incorporated into the organs of rabbits. As a result of dietary supplementation of 50 and 500 mg Ni/kg, Ni accumulated in the kidneys (4.9 +/- 0.5 and 17.1 +/- 3.1 vs. 1.9 +/- 0.3 mg/kg DM), ribs (10.3 +/- 0.4 and 10.4 +/- 0.6 vs. 9.1 +/- 0.6 mg/kg DM), heart (1.4 +/- 0.2 and 2.5 +/- 0.4 vs. 1.0 +/- 0.1 mg/kg DM) and liver (1.3 +/- 0.1 and 2.2 +/- 0.2 vs. 0.9 +/- 0.05 mg/kg DM), as compared to the control animals. It can be stated that supplementation of the diet with 50 mg Ni/kg had slight but non-significant beneficial effects on the growth performance of broiler chickens and rabbits.     

Toxicity, bioavailability and pharmacokinetics of a newly formulated colistin sulfate solution

We formulated a new colistin sulfate injectable solution and tested its effectiveness, toxicity and pharmacokinetics in vivo on mice, rabbits, and piglets. When intramuscularly injected (i.m.) into rabbits at 0.5 mL per site, the 2.5% colistin sulfate solution caused no reaction at the injection site, but the 5.0% solution caused the muscle circumference to appear erythematic. Tested LD50 in CD-1 mice were 38.72 mg/kg for i.m. and 431.95 mg/kg for oral administration, respectively. At 15.0 mg/kg/day (i.m.) for 5 days, colistin sulfate caused obvious neurotoxicity to piglets with moderate granular degenerations in the epithelial tissues from kidney and liver. These toxic responses were not seen when colistin sulfate was injected at 10.0 mg/kg/day for 5 days. Pharmacokinetic studies revealed Cmax of 3.73 +/- 0.28 and 6.40 +/- 0.18 microg/mL, Tmax of 32 +/- 1.5 and 34 +/- 1.8 min, t(1/2beta) of 256 +/- 14 and 264 +/- 29 min, and absolute bioavailability of 95.94 and 88.45% for colistin sulfate intramuscularly injected to piglets at 2.5 and 5.0 mg/kg, respectively. Serum colistin sulfate concentration followed a two-compartment open model showing first-order absorption. The high bioavailability and the long-lasting serum retention time indicated that the new solution is suitable for i.m. in piglets with a recommended dose of 2.5 mg/kg injected twice daily.     

长效土霉素注射液的急性毒性及肌肉刺激性研究

为考察新型长效土霉素注射液的安全性,分别对小白鼠和家兔进行急性毒性和局部刺激性试验。随机将60只小白鼠分为6组,每组10只,其中雌雄各半,进行急性毒性试验考察;随机将9只家兔分为3组,每组3只,进行局部刺激性试验。结果表明,该新型长效土霉素注射液小鼠肌肉注射LD 50为600.32 mg/kg,LD 50的95%的可信区间为(600.32±2.44)mg/kg;随着时间延长和给药剂量增加,刺激性增强,注射长效土霉素7 d后,家兔股四头肌出现红肿、发紫、坏死、光泽消失现象,15 d后肌肉组织的坏死范围扩大。该产品对小白鼠表现为低毒,对家兔的股四头肌有局部刺激性。     

乳酸恩诺沙星对小鼠的急性毒性试

采用新药乳酸恩诺沙星测定了其对实验小鼠的半数致死量（LD50）, 为其可溶性粉开展药效试验提供依据。按照农业部关于一般毒性试验及临床试验规范进行试验。结果表明, 乳酸恩诺沙星对小白鼠灌胃染毒及腹腔注射染毒的 LD50分别为3579 mg/kg,和571.3 mg/kg,其95％可信限分别为3011~4255 mg/kg和498.3~655.1 mg/kg。研究提示, 乳酸恩诺沙星属低毒物质,其可溶性粉能用于开展药效试验。     

乳酸恩诺沙星对小鼠的急性毒性试验

研究了乳酸恩诺沙星对小鼠的急性毒性,用寇氏法计算实验小鼠的半数致死量(LD50)和95%置信限。结果表明,乳酸恩诺沙星对小白鼠灌胃染毒及腹腔注射染毒的LD50分别为3579mg/kg和571.3mg/kg,其95%可信限分别为3011～4255mg/kg和498.3～655.1mg/kg。研究提示,乳酸恩诺沙星属低毒物质,其可溶性粉能用于开展药效试验。     

小鼠镉的蓄积性毒性试验研究

选用SPF级昆明种小鼠140只,做急性毒性和蓄积性毒性试验。通过急性毒性试验,得出Cd LD50为94.1 mg/kg体重。蓄积性毒性试验中,试验组小鼠每日灌胃染毒1次,Ⅰ组,1/10 LD50（Cd 9.41 mg/kg体重）;Ⅱ组,1/5 LD50（Cd 18.82 mg/kg体重）;Ⅲ组,1/3 LD50（Cd 31.36 mg/kg体重）;对照组Cd为 0 mg/kg体重,试验期4周。结果显示,染镉组小鼠生长发育落后于对照组（P<0.05或P<0.01）,组织镉残留量高于对照组（P<0.05或P<0.01）,肝细胞和肾小管上皮细胞变性,脾脏瘀血,并有明显的剂量—效应关系。     

烟酸黄藤素注射液安全性试验研究

为进一步临床试验并了解烟酸黄藤素注射液的安全性,对其进行了溶血性试验、肌肉刺激性试验和急性毒性试验（口服试验和腹腔注射试验）。结果表明,烟酸黄藤素注射液对兔红细胞不产生溶血和凝聚作用;肌肉注射,2只试验兔4块股四头肌刺激反应级之和为3,局部刺激反应轻微;口服、腹腔注射LD50分别为2866mg／kg、153mg／kg,黄藤素口服给药属低毒性药物,注射给药属中等毒性药物。     

A pharmacokinetic/pharmacodynamic approach vs. a dose titration for the determination of a dosage regimen: the case of nimesulide, a Cox-2 selective nonsteroidal anti-inflammatory drug in the dog

The present experiment was designed to determine a dosage regimen (dose, interval of administration) in the dog for nimesulide, a nonsteroidal anti-inflammatory drug with in vitro selectivity for the inhibition of cyclo-oxygenase 2 (Cox-2), using a pharmacokinetic/pharmacodynamic (PK/PD) approach. The PK/PD results were compared with those obtained using a classical dose titration study. In the PK/PD experiment, 11 dogs were subjected to Freund's adjuvant arthritis characterized by permanent hyperthermia. Nimesulide (5 mg/kg, oral route) was tested during the secondary phase of the inflammatory response. In the dose titration study, nimesulide (0, 3, 6 and 9 mg/kg, oral route) was tested in eight other dogs using a reversible urate crystal arthritis in a 4-period crossover design. Different PD endpoints (including lameness assessed by force plate and hyperthermia) were regularly measured during the PK/PD experiment, and plasma samples were obtained to determine the plasma nimesulide concentration. The data were modeled using an indirect effect model. The IC50 of nimesulide for lameness was 6.26 +/- 3.01 microg/mL, which was significantly higher than the EC50 value obtained for antipyretic effect (2.72 +/- 1.29 microg/mL). The ED50 estimated from the classical dose titration study were 1.34 mg/kg (lameness) and 3.0 mg/kg (skin temperature). The PK/PD parameters were used to simulate different dosage regimens (dose, interval of administration). The antipyretic and anti-inflammatory effects were calculated from the model for the recommended dosage regimen (5 mg/kg/24 h). It was apparent from this approach, that this dosage regimen enabled 76% of the theoretical maximal drug efficacy to be obtained for pyresis and 43% for lameness. It was concluded from the comparison of in vivo and in vitro IC50, that nimesulide is a potent NSAID for which some Cox-1 inhibition is required to obtain clinically relevant efficacy.     

Vergleich der histologischen Struktur der Kompakta der langen Röhren-knochen bei Maus, Hamster, Ratte, Meerschweinchen, Kaninchen, Katze und Hund während der Altersentwicklung

This paper reports on histological examinations of the diaphyseal structure of the long bones (humerus, radius, ulna, os femoris and tibia) of mouse, hamster, rat, guinea pig, rabbit, cat, and dog using six animals in three different age groups. There are considerable differences in structure between the species. The results show that with increasing height in the evolution of the species and period of life, as well as advancing age, the differentiation and complexity of bone structures increases. The differences in structure between the localization of bones within the individual species are not considerable. The species comparison results in great similarities between the bone structures of each of mouse and hamster, of rat and guinea pig, as well as of cat and dog. The bone structure of the animals examined becomes more similar to the human structure from mouse, hamster, rat, guinea pig, rabbit, and cat to dog.     

国产硫酸头孢喹肟对小鼠的急性和蓄积毒性研究

为了研究国产硫酸头孢喹肟对昆明小鼠的急性毒性和蓄积毒性,采用改良寇氏法测定国产硫酸头孢喹肟的LD50;以剂量定期递增法计算蓄积系数,并于给药后第21天给予试验组和对照组小鼠1 LD50的量,观察各组小鼠对硫酸头孢喹肟的耐受性。结果表明,国产硫酸头孢喹肟原料药对小鼠口服LD50大于5 000 mg/kg,其混悬液制剂对小鼠腹腔注射LD50为844.03 mg/kg,LD50的95%可信限为802.05 mg/kg~887.56 mg/kg;蓄积试验中无小鼠死亡,蓄积系数K>5.3;耐受性试验显示,试验组死亡率(10%)显著低于对照组(40%)(P<0.05)。由此可见,国产硫酸头孢喹肟毒性低,临床使用安全,对小鼠没有蓄积毒性,小鼠对本品可产生明显耐受性。     

阿维菌素微囊对大鼠急性和亚慢性毒性试验

探讨阿维菌素微囊的安全性,为临床研究提供试验依据,以大鼠作为研究对象,采用腹腔注射法进行了急性和亚慢性毒性试验。结果表明,阿维菌素微囊的半数致死量(LD50)为31.73 mg/kg,与普通注射剂相比大了113%;再以1/10、1/20和1/50 LD50(高、中、低剂量组)给大鼠用药,连续腹腔注射21 d,给药部位未见异常,低剂量组血液生理生化指标正常,各实质性器官细胞未见组织学病变;高、中剂量组出现体重增长缓慢、行动迟缓等异常情况,停药2周后恢复正常。说明阿维菌素经微囊化后毒性明显降低,该制剂基本安全,可用于临床研究。     

Control of radiation-induced emesis with promethazine, cimetidine, thiethylperazine, or naloxone

Promethazine (2 mg/kg), cimetidine (4 mg/kg), thiethylperazine (0.86 mg/kg), and naloxone (0.08 mg/kg) were each evaluated for their ability to increase the threshold of radiation-induced emesis in the dog. Each dog was fed a can of dog food (ca 0.4 kg) and then injected IM with the appropriate drug 1 hour before being irradiated by a 60Co teletherapy unit. The total radiation dose given an individual dog was determined by an up-and-down exposure schedule. Dogs were then observed continuously for 10 hours while the number, time of onset, and duration of each emetic episode were monitored. The dose of radiation causing emesis in 50% (ED50 +/- SEM) of control dogs was 170 +/- 38.5 rad. The ED50 +/- SEM was increased to 402 +/- 18.6 rad by promethazine, to 331 +/- 27.3 rad by cimetidine, and to 320 +/- 38.5 rad by thiethylperazine. This increased tolerance was significant at P less than 0.05 for each drug. The ED50 for naloxone was 262.5 +/- 92.9 rad, which was not a statistically significant increase in threshold.     

Fonofos toxicosis in dairy cows: an accidental poisoning (1977)

An accidental poisoning (in 1977) of 28 Holstein cows occurred when approximately 0.9 kg of 25% active ingredient fonofos, O-ethyl S-phenyl ethylphosphonothiolothionate, was spilled onto bulk feed in a delivery truck. Eight cows died within 2 days; the remaining 20 were necropsied 29 days later. Of the 8 fatally poisoned, 7 were being fed a high-grain diet and 1 was fed a medium-grain diet. Fonofos concentrations in feed cart and storage bin samples were 100 micrograms/g and 61 micrograms/g, respectively. Tissues from 6 animals were analyzed extensively for fonofos concentrations: 2 had died immediately; the other 4 were in the recovery state when they were necropsied. Rumen contents and liver, kidney, brain, heart, and milk samples were analyzed. Fonofos concentrations in these samples were significantly higher in the cows fatally affected than in the cows necropsied 3 weeks later. The oral acute LD50 and LD1 of fonofos in Holstein cows were calculated by the Litchfield and Wilcoxon method to be 1.30 and 0.84 mg/kg, respectively, with a 95% confidence range of +/- 0.20 mg/kg.     

兔出血症病毒两种感染途径的致死性比较研究

为提高猪瘟活疫苗的外源性兔出血症病毒(RHDV)的检测敏感性,进行了RHDV对家兔感染途径的致死性比较试验,以便筛选出具有较高致死性的感染途径。将RHDV通过皮下、静脉两种途径感染家兔,比较了家兔两种感染途径的半数致死量(LD_(50)),同时对1批污染RHDV的脾淋源猪瘟活疫苗采用皮下、静脉两种途径注射家兔进行RHDV检测。结果表明,静脉途径对家兔的LD_(50)是皮下途径的126倍;污染疫苗的检测应用也表明家兔感染的静脉途径比皮下途径更加敏感,提高了猪瘟活疫苗外源性RHDV污染的检出率;RT-PCR证实了注苗死亡家兔的肝脏组织含有RHDV。本试验可为《中国兽药典》的修订提供数据参考。     

狗舌草总黄酮的提取及其毒性试验

从狗舌草中提取分离到黄酮类化合物并测定其含量 ,用改良寇氏法测定总黄酮的小鼠LD50 为 ( 1392 52± 94 6 2 )mg/kg ,属于中等毒范围。初步表明其与临床牧区的狗舌草中毒病相关不大 ,可能与狗舌草的抗癌、抑癌作用有关     

苦豆子总碱对小鼠急性毒性试验研究

采用改良寇氏法测定苦豆子总碱提取物对小鼠腹腔注射的急性毒性,评价其安全性,为临床安全用药提供依据。给试验组小鼠灌服不同浓度的苦豆子总碱提取物,观察给药后小鼠的临床表现与死亡情况,采用改良寇氏公式计算LD50及LD50的95%可信限,结果表明,苦豆子总碱经腹腔注射的LD50为559.24 mg/kg,95%可信限为471.95-663.59 mg/kg。试验结果提示,苦豆子总碱的毒性较低,临床用药安全可靠。     

高效氯氰菊酯乳油对雄性家兔精液品质的影响

采用4.5%高效氯氰菊酯乳油喷洒饲草,使4组家兔每日每千克体重染毒高效氯氰菊酯分别为0mg、1.5mg、3.0mg、4.5mg,持续56d后采用常规方法对精液品质进行检查。结果各剂量组家兔体重、睾丸重量、精液量及其pH等方面均无显著性差异(>0.05);与对照组相比,1.5mg/kg体重试验组的精子密度、精子活力、畸形率无明显变化(>0.05),但3.0mg/kg、4.5mg/kg剂量组则发生显著变化(<0.05)。表明当家兔高效氯氰菊酯染毒量达到3.0mg/kg体重时即可导致家兔精子密度、精子活力、畸形率等方面发生异常,对家兔具有一定的生殖毒性。     

连翘酯苷对体外培养细胞的毒性研究

探讨了连翘酯苷对体外培养细胞的毒性,以期为人们更好地研究利用连翘酯苷提供实验依据。实验采用细胞病变法观察连翘酯苷对猪肾细胞（PK-15）、猴肾细胞（Mare-145）、鸡胚肾细胞（CEK）、鸡外周血淋巴细胞（PBL）等4种细胞的形态损伤;用MTT法检测连翘酯苷作用这4种细胞后的细胞活性和细胞数量的变化。根据这两种方法的结果计算出连翘酯苷对这4种细胞的半数致死量。实验结果显示高剂量的连翘酯苷可致细胞发生病变,而低剂量组的细胞形态优于对照组。经SPSS16．0统计,连翘酯苷对PK-15、Mare-145、CEK3种细胞的半数致死量分别为137．8、87．1、384．4μg／mL,对PBL应用到中华人民共和国兽药典（2000年版）规定药量的10倍剂量,结果未发现致死性。因此,适当合理的连翘酯苷用量对体外培养的细胞没有毒性,反而有一定的维持细胞形态的营养作用和刺激细胞增殖的作用。